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Dual regulation of atrial natriuretic factor‐dependent guanylate cyclase activity by ATP
Author(s) -
Marala Ravi B.,
Sitaramayya Ari,
Sharma Rameshwar K.
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)80361-6
Subject(s) - guanylate cyclase 2c , gucy1b3 , gucy1a3 , gucy2d , npr2 , npr1 , cyclase , chemistry , receptor , cofactor , biochemistry , guanylate cyclase , adenylate kinase , second messenger system , enzyme , medicine , natriuretic peptide , heart failure
The ‘second messenger’ of certain atrial natriuretic factor (ANF) signals is cyclic GMP. One type of ANF receptor linked to the synthesis of cyclic GMP is a transmembrane protein which contains both the ANF‐binding and guanylate cyclase activities. The consensus is that the maximal activity or this guanylate cyclase is observed in the presence of ATP. We now show that depending upon the cofactors Mg 2+ or Mn 2+ , ATP stimulates or inhibits the ANF‐dependent guanylate cyclase activity in the testicular plasma membranes; stimulation in the presence of Mg 2+ and inhibition in the presence of Mn 2+ . With Mg 2+ as cofactor neither ATP nor ANF stimulate the cyclase activity — it is only when the two are together that the enzyme is activated. Furthermore, this investigation for the first time demonstrates binding of ATP to the ANF receptor guanylate cyclase, suggesting that ATP‐mediated responses could occur by direct ATP binding to the cyclase.